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ADAM8 inactivation retards intervertebral disc degeneration in mice

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Genes & Diseases 2024年第3期11卷 91-94页

作者： Zuozhen Tian Frances S.Shofer Mingyue Fan Alec Z.Sandroni Lutian Yao Lin Han Ling Qin Motomi Enomoto-lwamoto Yejia Zhang Department of Physical medicine&Rehabilitation Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA19146USA Department of Emergency medicine Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Orthopedic Surgery Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA school of Biomedical Engineering Science&Health SystemsDrexel UniversityPhiladelphiaPA 19104USA Department of Orthopedics/Sports medicine and Joint Surgery the First Hospital of China Medical UniversityShenyangLiaoning 110001China Department of Orthopedics University of Maryland School ofMedicineBaltimoreMD21201USA Section of Rehabilitation medicine Corporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPA 19104USA

ADAM8 has been identified as the fibronectin-cleaving enzyme in human degenerative intervertebral disc(IVD)tissues.^(1)Increase of the active form of ADAM8 and its cleavage product,fibronectin fragment,correlated with an increased degree of IVD degeneration.1 Furthermore,fibronectin fragments have been shown to accelerate the progression of IVD degeneration.^(2)These findings suggest that ADAM8 may play a role in degenerative disc disease,a clinical problem with tremendous socioeconomic burdens in the United States.

关键词： ADAM8 degeneration intervertebral

Polystyrene nanoplastics induce glycolipid metabolism disorder via NF-κB and MAPK signaling pathway in mice

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Journal of Environmental Sciences 2024年第3期137卷 553-566页

作者： Xingpei Fan Xiaoyan Li Jiaxin Li Yuxia Zhang Xiangjuan Wei Hailong Hu Boya Zhang Haining Du Meimei Zhao Ruijiao Zhu Daqian Yang Yuri Oh Ning Gu school of Life Science and Technology Harbin Institute of TechnologyHarbin 150001China State Key Laboratory of Urban Water Resource and Environment Harbin Institute of TechnologyHarbin 150006China Department of medicine Renal Electrolyte and Hypertension DivisionDepartment of GeneticsPerelman School of MedicineUniversity of PennsylvaniaPhiladelphia 19104USA Faculty of Education Wakayama UniversityWakayama 640-8441Japan

Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread ***,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at ***,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling *** PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor *** activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and *** activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin *** parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγ***,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were *** treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in *** on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.

关键词： Nanoplastics Resveratrol Hyperglycemia Lipid metabolism Infammatory response Reactive oxygen species(ROS)

Modern internet search analytics and thyroidectomy:What are patients asking?

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 49-58页

作者： Neeraj Suresh Christian Fritz Emma De Ravin Karthik Rajasekaran Department of Otorhinolaryngology–Head&Neck Surgery University of PennsylvaniaPhiladelphiaPennsylvaniaUSA perelman school of medicine at the University of Pennsylvania PhiladelphiaPennsylvaniaUSA Leonard Davis Institute of Health Economics University of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Objectives:Thyroidectomy is among the most commonly performed head and neck surgeries,however,limited existing information is available on topics of interest and concern to *** Design:***:***:A search engine optimization tool was utilized to extract metadata on Google‐suggested questions that“People Also Ask”(PAA)pertaining to“thyroidectomy”and“thyroid surgery.”These questions were categorized by Rothwell criteria and topics of *** Journal of the American Medical Association(JAMA)benchmark criteria enabled quality ***:A total of 250 PAA questions were ***‐oriented PAA questions describing what to expect during and after the surgery on topics such as postoperative management,risks or complications of surgery,and technical details were significantly less popular among the“thyroid surgery”group(P<0.001,P=0.005,and P<0.001,respectively).PAA questions about scarring and hypocalcemia were nearly threefold more popular than those related to pain(335 and 319 vs.113 combined search engine response page count,respectively).The overall JAMA quality score remained low(2.50±1.07),despite an increasing number of patients searching for“thyroidectomy”(r(77)=0.30,P=0.007).Conclusions:Patients searching for the nonspecific term“thyroid surgery”received a curated collection of PAA questions that were significantly less likely to educate them on what to expect during and after surgery,as compared to patients with higher health literacy who search with the term“thyroidectomy.”This suggests that the content of PAA questions differs based on the presumed health literacy of the internet user.

关键词： information quality online health education search analytics thyroid surgery thyroidectomy

Effect of drug therapies on self-reported chemosensory outcomes after COVID-19

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 88-96页

作者： Marco A.Fornazieri Bruno M.Cunha Samuel P.Nicácio Lucas K.Anzolin JoséL.B.da Silva Aristides Fernandes Neto Deusdedit Brandão Neto Richard L.Voegels Fábio D.R.Pinna Department of Surgery Londrina State UniversityLondrinaBrazil Department of medicine Pontifical Catholic University of ParanáLondrinaBrazil Department of Otorhinolaryngology University of São PauloSao PauloBrazil Department of Otorhinolaryngology:Head and Neck Surgery Perelman School of MedicineSmell and Taste CenterUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Objective:The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection on self-reported alterations in taste and/or smell ***:Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019(post-COVID-19)chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the *** dependent measure—self-reported total recovery of chemosensory symptoms—was subjected to stepwise logistic *** predictors included demographic and clinical variables,in addition to specific medications used to mitigate disease symptoms(i.e.,systemic corticosteroids,oseltamivir,vitamin C,ibuprofen,hydroxychloroquine,azithromycin,ivermectin,nitazoxanide,anticoagulants,and zinc).Results:The median time between COVID-19 symptom onset and the interviews was 81 days(interquartile range:60-104).Of the 714 subjects,249(34.9%)reported total recovery of their chemosensory function;437(61.2%)had at least one treatment since the beginning of the *** and those with more comorbidities had undergone more *** recovery rates of the treated and nontreated groups did not differ ***,respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell *** who took oral zinc were less likely to ***:No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal,although nitrazoxide trended in a positive *** zinc had a negative effect on the reported recovery of these senses.

关键词： chemosensory disorder coronavirus infections COVID-19 drug therapy SARS-CoV-2 smell loss taste loss

First 150 years of catatonia:Looking back at its complicated history and forward to the road ahead

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World Journal of Psychiatry 2024年第5期14卷 600-606页

作者： Levente Csihi Gabor S Ungvari Stanley N Caroff Gábor Gazdag Department of Psychiatry and Psychiatric Rehabilitation Jahn Ferenc South Pest HospitalBudapest 1204Hungary Division of Psychiatry School of MedicineUniversity of Western AustraliaCrawley 6009Western AustraliaAustralia Section of Psychiatry University of Notre DameFremantle 6160Western AustraliaAustralia Behavioral Health Service Corporal Michael J CresenczVeterans Affairs Medical CenterPhiladelphiaPA 19104United States Department of Psychiatry University of PennsylvaniaPerelman School of MedicinePhiladelphiaPA 19104United States Department of Psychiatry and Psychotherapy Faculty of MedicineSemmelweis UniversityBudapest 1083Hungary

Karl Ludwig Kahlbaum(1828-1899)was the first to conceptualize and describe the main clinical features of a novel psychiatric illness,which he termed catatonia in his groundbreaking monograph published 150 years *** Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course,a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical *** his classification system,Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox(schizophrenia)disease *** of the substantial influence of Kraepelin’s classification,catatonia was predominantly perceived as a component of schizophrenia for most of the 20th ***,with the advent of the psychopharmacotherapy era starting from the early 1950s,interest in catatonia in both clinical practice and research subsided until the early *** past two decades have witnessed a resurgence of interest in *** Diagnostic and Statistical Manual of Mental Disorders Fifth Edition,marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical *** introduction of an independent diagnostic category termed“Catatonia Not Otherwise Specified”significantly stimulated research in this *** authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.

关键词： Catatonia Historical overview Psychopharmacology Diagnostic and Statistical Manual of Mental Disorders-5 Wernicke-Kleist-Leonhard school

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military Medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang Gao Wei Sun Jun-You Li Cheng Wang Qing-Yu Zhang Zhi-Zhuo Li Peng Xu Department of Joint Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China Department of Orthopaedic Surgery of the perelman school of medicine University of PennsylvaniaPhiladelphiaPA 19104USA school of Mechanical Engineering Sungkyunkwan UniversitySuwon 16419South Korea Department of Orthopaedic Surgery Peking University Third HospitalPeking UniversityBeijing 100191China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life ***,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of *** fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo ***,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

Optical redox imaging of ANT1-de-cient muscles

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing Zhao Douglas Wallace Lin Z.Li Britton Chance Laboratory of Redox Imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Center for Mitochondrial and Epigenomic medicine Children's Hospital of Philadelphia Research Institute Philadelphia PA 19104USA Center for Biostatistics and Epidemiology Lewis Katz school of medicine at Temple University Philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** Chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

IgSF11-mediated phosphorylation of pyruvate kinase M2 regulates osteoclast differentiation and prevents pathological bone loss

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Bone Research 2023年第1期11卷 215-227页

作者： Hyunsoo Kim Noriko Takegahara Yongwon Choi Department of Pathology and Laboratory medicine University of Pennsylvania Perelman School of MedicinePhiladelphiaPA19104USA

Osteoclasts are primary bone-resorbing cells,and receptor-activated NF-k B ligand(RANKL)stimulation is the key driver of osteoclast *** late-stage differentiation,osteoclasts become multinucleated and enlarged(so-called“maturation”),suggesting their need to adapt to changing metabolic demands and a substantial increase in ***,we demonstrate that immunoglobulin superfamily 11(Ig SF11),which is required for osteoclast differentiation through an association with the postsynaptic scaffolding protein PSD-95,regulates osteoclast differentiation by controlling the activity of pyruvate kinase M isoform2(PKM2).By using a system that directly induces the activation of Ig SF11 in a controlled manner,we identified PKM2 as a major Ig SF11-induced tyrosine-phosphorylated *** SF11 activates multiple Src family tyrosine kinases(SFKs),including c-Src,Fyn,and Hc K,which phosphorylate PKM2 and thereby inhibit PKM2 ***,Ig SF11-deficient cells show higher PKM2activity and defective osteoclast ***,inhibiting PKM2 activities with the specific inhibitor Shikonin rescues the impaired osteoclast differentiation in Ig SF11-deficient cells,and activating PKM2 with the specific activator TEPP46 suppresses osteoclast differentiation in wild-type ***,PKM2 activation further suppresses osteoclastic bone loss without affecting bone formation in *** together,these results show that Ig SF11 controls osteoclast differentiation through PKM2 activity,which is a metabolic switch necessary for optimal osteoclast maturation.

关键词： SF11 osteoclast impaired

Novel data-driven subtypes and stages of brain atrophy in the ALS-FTD spectrum

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Translational Neurodegeneration 2023年第1期12卷 50-69页

作者： Ting Shen Jacob W.Vogel Jeffrey Duda Jeffrey S.Phillips Philip ACook James Gee Lauren Elman Colin Quinn Defne A.Amado Michael Baer Lauren Massimo Murray Grossman David J.Irwin Corey T.McMillan Penn Frontotemporal Degeneration Center Department of NeurologyPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Clinical Sciences SciLifeLabLund University22242 LundSweden Penn Image Computing and Science Lab(PICSL) Department of RadiologyPerelman School of MedicineUniversity of Penn-sylvaniaPhiladelphiaPA 19104USA Department of Neurology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Digital Neuropathology Laboratory Department of NeurologyPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA.

Background TDP-43 proteinopathies represent a spectrum of neurological disorders,anchored clinically on either end by amyotrophic lateral sclerosis(ALS)and frontotemporal degeneration(FTD).The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes,highlighting its *** study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD *** We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD(bvFTD;with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants),103 ALS,and 47 ALS-FTD patients with likely TDP-43.A Subtype and Stage Inference(SuStaIn)model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns,and we related subtypes and stages to clinical,genetic,and neuropathological features of *** SuStaIn identified three novel subtypes:two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions,and a normal-appearing group without obvious brain *** limbic-predominant subtype tended to present with more impaired cognition,higher frequencies of pathogenic variants in TBK1 and TARDBP genes,and a higher proportion of TDP-43 types B,E and *** contrast,the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type *** normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients,higher cognitive capacity,higher proportion of lower motor neuron onset,milder motor symptoms,and lower frequencies of genetic pathogenic *** overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration,higher King’s stage,and cog

关键词： Amyotrophic lateral sclerosis Frontotemporal degeneration Disease heterogeneity SuStaIn model